*5.2.1 Medical nutrition therapy*

Medical nutrition therapy is based on healthy eating principles. Its goals are to promote and support healthful eating patterns, with various nutrient-dense foods


*ambulatory glycemic profile per day [19, 49]. \*Not a goal but indicates a lower risk.*

#### **Table 1.**

*Therapeutic targets in T2DM (adapted by [12, 19, 48, 49]).*

in appropriate portion sizes. To ensure adherence and effectiveness, nutritional interventions should be individualized by meeting individual's needs, personal and cultural preferences, access to healthy foods, the pleasure of eating, and providing practical tools to implement the recommendations [50].

Dietary interventions can reduce HbA1c with up to 2% [50]. Caloric intake should be adapted to maintain body weight control. General recommendations are to avoid saturated lipids and foods with a high glycemic index. The Mediterranean diet, the DASH diet (Dietary Approaches to Stop Hypertension), plant-based diets, are recommended for their proven benefits. Carbohydrates should come from foods rich in fibers: vegetables, legumes, whole grains, fruits. Lipids should be mainly monoand polyunsaturated and omega-3. Supplementation with minerals or vitamins is only recommended in case of deficiency. Hydration is important, with the selection of non-caloric drinks. Consumption of alcohol in moderate amounts is acceptable, but special attention should be paid to the risk of hypoglycemia, hyperglycemia and additional caloric intake. Sodium intake should be <2,300 mg/day [50].

**285**

**Table 2.**

*Cardiovascular Risk/Disease in Type 2 Diabetes Mellitus DOI: http://dx.doi.org/10.5772/intechopen.97422*

also an important recommendation [50].

*5.3.1 Pharmacotherapy of hyperglycemia*

Most patients' recommended physical activity is at least 150 minutes/week, at least three times/week, moderate/high intensity, aerobic, 2–3 sessions/week of endurance and flexibility exercises. Reducing the time spent in sedentary lifestyle is

The pharmacotherapy of hyperglycemia should be patient-centred, addressed to reduce glycemia and the overall CVR [53]. Metformin remains the first step of the treatment. It is initiated simultaneously with lifestyle optimization, from the diagnosis, and is continued throughout the treatment, associated with the other therapeutic classes. It is stopped in case of intolerance and at an eGFR <30 mL/

risk, established kidney disease, or heart failure, the guidelines recommend the medication with demonstrated CVD benefit, independent of the HbA1c value: SGLT-2 inhibitor (sodium-glucose cotransporter 2 inhibitor – empagliflozin, canagliflozin, dapagliflozin) or GLP-1RA (glucagon-like peptide 1 receptor agonist – semaglutide, liraglutide, dulaglutide, long-acting exenatide, lixisenatide)

For patients without the conditions mentioned above, a second or third agent's choice as an add-on to metformin is based on CV safety, the effect on body weight, and avoidance of hypoglycemia. Sulfonylureas have controversial CV effects. To date, the ADVANCE study (Action in Diabetes and Vascular Disease: Preterax

> HR = 0.78 (0.66–0.93)

> HR = 0.62 (0.49–0.77)

HR = 0.78 (0.67–0.91) (CV mortality and hHF)

(0.73–0.95) (CV mortality and hHF)

NS HR = 0.83

HR = 0.87 (0.78–0.97)

HR = 0.74 (0.58–0.95) \*

HR = 0·88 (0·79–0·99)

HR = 0.86 (0.74–0.99)

HR = 0.86 (0.75–0.97)

*Antihyperglycemic agents with proven CVD/CKD/hHF benefits [12, 19, 53–59].*

. For patients with established ASCVD or indicators of high ASCVD

**MACE CV mortality hHF Renal effects**

NS HR = 0.78

NS NS HR = 0.64

NS NS HR = 0·85

HR = 0.65 (0.50–0.85)

HR = 0.67 (0.52–0.87)

HR = 0.73 (0.61–0.88) (0.67–0.92)

(0.46–0.88)

(0·77–0·93)

HR = 0.61 (0.53–0.70)

HR = 0.60 (0.47–0.77)

HR = 0.53 (0.43–0.66)

*5.2.2 Physical activity*

**5.3 Pharmacotherapy**

min/1.73 m<sup>2</sup>

(**Table 2**) [12, 19, 53–59].

**GLP-1 RA/Study**

Liraglutide (LEADER) [54]

Semaglutide (SUSTAIN) [55]

Dulaglutide (REWIND) [56]

Canagliflozin (CANVAS) [58]

Dapagliflozin (DECLARE-TIMI 58) [59]

**SGLT2-inh/Study** Empagliflozin (EMPAREG-OUTCOME) [57]
